{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:08:15Z","timestamp":1790795295469,"version":"4.1.0"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T00:00:00Z","timestamp":1668556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T00:00:00Z","timestamp":1668556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"New National Excellence Program","award":["\u00daNKP-21-3-II-SE-13"],"award-info":[{"award-number":["\u00daNKP-21-3-II-SE-13"]}]},{"name":"New National Excellence Program","award":["\u00daNKP-21-5-SE-3"],"award-info":[{"award-number":["\u00daNKP-21-5-SE-3"]}]},{"name":"J\u00e1nos Bolyai Research Scholarship of the Hungarian Academy of Sciences","award":["BO\/00451\/20\/5"],"award-info":[{"award-number":["BO\/00451\/20\/5"]}]},{"DOI":"10.13039\/501100002332","name":"Semmelweis University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002332","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Immunol Immunother"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Introduction<\/jats:title>\n                <jats:p>Immune checkpoint inhibitors (ICI) such as anti-PD-L1 and anti-PD-1 agents have been proven to be effective in various cancers. However, the rate of non-responders is still high in all cancer entities. Therefore, the identification of biomarkers that could help to optimize therapeutic decision-making is of great clinical importance. Soluble PD-L1 (sPD-L1) and PD-1 (sPD-1) are emerging blood-based biomarkers and were previously shown to be prognostic in various clinical studies.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Objective<\/jats:title>\n                <jats:p>We aimed to evaluate the prognostic relevance of sPD-L1 and sPD-1 in patients with different tumor entities who underwent ICI therapy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We searched for articles in PubMed via Medline, Embase, Scopus, and Cochrane databases. The primary outcome was overall survival (OS) and progression-free survival (PFS); furthermore, we analyzed on-treatment serum level changes of sPD-L1 and sPD-1 during ICI therapy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We synthesized the data of 1,054 patients with different cancer types from 15 articles. Pooled univariate analysis showed that elevated levels of sPD-L1 were significantly associated with inferior OS (HR\u2009=\u20091.67; CI:1.26\u20132.23, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u200979%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). The strongest association was found in non-small cell lung cancer, whereas weaker or no association was observed in melanoma as well as in renal cell and esophageal cancers. Pooled multivariate analysis also showed that elevated levels of sPD-L1 correlated with worse OS (HR\u2009=\u20091.62; CI: 1.00\u20132.62, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u200984%, <jats:italic>p<\/jats:italic>\u2009=\u20090.05) and PFS (HR\u2009=\u20091.71; CI:1.00\u20132.94, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u200982%, <jats:italic>p<\/jats:italic>\u2009=\u20090.051). Furthermore, we observed that one or three months of anti-PD-L1 treatment caused a strong (27.67-fold) elevation of sPD-L1 levels in malignant mesothelioma and urothelial cancer.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We found significantly inferior OS in ICI-treated cancer patients with elevated pre-treatment sPD-L1 levels, but this association seems to be tumor type dependent. In addition, sPD-L1 increases during anti-PD-L1 therapy seems to be therapy specific.\n<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00262-022-03328-9","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T17:04:57Z","timestamp":1668618297000},"page":"1061-1073","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Pre-treatment soluble PD-L1 as a predictor of overall survival for immune checkpoint inhibitor therapy: a systematic review and meta-analysis"],"prefix":"10.1007","volume":"72","author":[{"given":"\u00c1d\u00e1m","family":"Sz\u00e9les","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"Fazekas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szilard","family":"V\u00e1ncsa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda","family":"V\u00e1radi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra Ter\u00e9zia","family":"Kov\u00e1cs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Krafft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Gr\u00fcnwald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Hadaschik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Csizmarik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e9ter","family":"Hegyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"V\u00e1radi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e9ter","family":"Nyir\u00e1dy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tibor","family":"Szarvas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,16]]},"reference":[{"key":"3328_CR1","doi-asserted-by":"publisher","first-page":"4592","DOI":"10.1158\/1078-0432.CCR-18-1538","volume":"25","author":"DB Doroshow","year":"2019","unstructured":"Doroshow DB, Sanmamed MF, Hastings K, Politi K, Rimm DL, Chen L, Melero I, Schalper KA, Herbst RS (2019) Immunotherapy in non-small cell lung cancer: facts and hopes. 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The other authors report none to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"No ethical approval was required for this systematic review with meta-analysis, as all data were already published in peer-reviewed journals. Furthermore, no patients were involved in the design, conduct, or interpretation of our study. The datasets used in this study can be found in the full-text articles included in the systematic review and meta-analysis.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}